Aspects of the Amlodipine Pleiotropy in Biochemistry, Pharmacology and Clinics

Amlodipine is the third generation calcium antagonist, 1,4-dihydropyridine derivative with the prolonged duration of the antihypertensive action, especially blocking L-type Ca ion channels. It promotes beneficial therapeutic effect by coronary and other blood vessel diseases and thus delays development of the atherosclerosis. It has several known trade names, the most mentioned is Norvasc. Amlodipine is well tolerated in the clinics, it could be used in combinations with other drugs – diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, statins. Amlodipine at nanomolar concentrations binds to the voltage-dependent L-type calcium channels. It possesses optimal lipophylicity. Amlodipine also influences the NO-dependent metabolic processes, stimulates NO synthesis and prolongs NO action duration. Results of the studies of the amlodipine pharmacological and clinical properties are summarized in several reviews. The present review contains opinion from the scientific works of the last decades about the multisided or pleiotropic amlodipine mechanisms of action, it contains information about sometimes controversial clinical studies of the amlodipine vasoand cardioprotective activity. INTRODUCTION: Amlodipine is the third generation calcium antagonist, 1, 4-dihydropyridine (1, 4-DHP) compound with prolonged action. It has expressed properties of Ca channel (especially L-type and Ttype) blockers (CCB). Besides, it exerts multisided (pleiotropic, namely, when a drug has actions other than those for which the compound was specifically indicated or developed) effects on other metabolic processes. It is the basis for the beneficial therapeutic action at heart and vasculature diseases and delays the development of atherosclerosis 1 . This drug is well tolerated by patients. It has no significant side effects. It could be used in the monotherapy, as well in combination with other drugs-diuretics, angiotensineconverting enzyme (ACE) inhibitors, antagonists of the angiotensine II receptors, statins 12, 13, 14, . Amlodipine at nanomolar concentrations binds to the voltage-dependent L-type calcium channels. It has optimal lipophylicity, and it has a free aminogroup, which garantees the good bioavailability . Amlodipine also influences the NO-dependent metabolic processes too, it stimulates NO synthesis and prolongs NO action duration . Results of the studies of amlodipine pharmacological and clinical properties are summarized in several reviews 9, 12, 17 . This review summarizes outlook about experimental materials from the last decades concerning amlodipine pleiotropy in the action mechanism, as well sometimes controversial clinical observations about its cardioprotective and vazoprotective action.